CN105012294A - New uses of ellagic acid compound in preparation of hyperuricemia treating drug - Google Patents
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Abstract
The present invention discloses uses of an ellagic acid derivatives and a pharmaceutically acceptable salt in hyperuricemia treatment. According to the present invention, the ellagic acid compound provides a strong in vitro inhibition effect on xanthine oxidase, can significantly reduce the serum uric acid level in the hyperuricemia mice, and can be used as the potential xanthine oxidase inhibitor and the uric acid lowering drug for treatment of hyperuricemia and gout or gout complications caused by hyperuricemia.
Description
Technical field
The invention belongs to chemical medicine, be specifically related to a kind of ellagic acid analog derivative and the application of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof, and a kind of pharmaceutical composition for the treatment of hyperuricemia and gout.
Background technology
In recent years, along with the raising of people's living standard, dietary structure changes, and the intake of sugar, fat, protein obviously increases, and the sickness rate of hyperuricemia and gout increases day by day, and oneself becomes a kind of commonly encountered diseases.
Be hyperuricemia when it is generally acknowledged blood uric acid 416 μm of ol/L, about 5% l2% Patients with Hyperuricemia can develop into gout.Clinical characters is: gouty acute arthritis recurrent exerbation, tophaceous deposition, characteristic chronic arthritis and joint deformity, often involves kidney and causes chronic interstitial nephritis and kidney urate calculus to be formed.The acute attack of gout is that Monosodium urate (monosodium urate crystal, MSU) organizes the acute inflammatory reaction depositing in crystalline form and cause in joint and periarticular.Gout not only can invade bone and joint, but also easily involves kidney and cardiovascular system.Hyperuricemia and the disease such as primary gout and obesity, hyperlipemia, hypertension, diabetes, atherosclerosis are remarkable positive correlation.Therefore, hyperuricemia is a kind of serious metabolic disease of harm humans health.Uric acid level in suitable control blood is prevention, to improve with gout be hyperuricemia basic of representative.
At present, the control of uric acid in blood is mainly realized by following two kinds of approach: (1) suppresses the generation of uric acid.Uric acid is generated through the effect of xanthine oxidase by hypoxanthine and xanthine, and the xanthine oxidase above-mentioned reaction that is catalysis and then generate the necessary enzyme of uric acid, therefore, suppress xanthine oxidase (xanthine oxidase, XO) activity effectively can suppress the formation of uric acid, and then plays the effect of the symptoms such as treatment gout.The medicine of suppression uricopoiesis conventional at present has allopurinol, Febuxostat etc.; (2) excretion of uric acid is promoted.The medicine of promotion urate excretion conventional at present has probenecid, benzbromarone etc.
Above-mentioned two kinds of modes all can play the effect reducing uric acid in blood, and then curative effect is produced to diseases such as gout, arthritis, subcutaneous gout calculus, kidney stone or gouty nephropathies that hyperuricemia causes, but said medicine toxic and side effects is usually larger, such as, allopurinol can cause the serious toxic and side effects such as allergy (sickness rate 10 15%), super quick syndrome, bone marrow depression; Probenecid, benzbromarone then have stimulating gastrointestinal road, cause renal colic, excite the side effect such as gout acute attack, limit the clinical practice of these medicines to a certain extent.
Ellagic acid is extensively present in a kind of natural polyphenol in the plant tissues such as various mushy fruit, nut, and it is the dimerization derivant of gallic acid, is a kind of polyphenol dilactone.Ellagic acid has multiple bioactive functions to have report to point out, such as anti-oxidation function, anticancer, mutation performance (Li Suqin, Yuan Qipeng. the physiological function of ellagic acid and process exploitation present Research [J]. research and development of natural products, 2001,13 (5): 71 74.).Domestic and international to the research positive develop rapidly of ellagic acid as anticarcinogen and coagulant at present, the physiological action of ellagic acid and the research of mechanism thereof more and more come into one's own.But to the research rarely found report of Ellagic Acid Derivatives, bibliographical information Ellagic Acid Derivatives has certain xanthine oxidase inhibitory activity, its result display ellagic acid and Rou Hua Suan 4 O β D xylopyranoside suppress xanthine oxidase IC
50value is respectively 9.3,4.7 μm of ol/L.But the ellagic acid analog derivative kind that document report extracts is few, is only separated and obtains ellagic acid and ellagic acid xylopyranoside.The present invention carries out extraction and isolation to vegetable hair Fructus Chebulae, obtain miscellaneous ellagic acid analog derivative, and the majority of compounds that separation obtains suppresses xanthine oxidase activity to be significantly increased relative to ellagic acid, obtains the ellagic acid analog derivative that multiple inhibition is better than ellagic acid and ellagic acid xylopyranoside.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of ellagic acid compounds and pharmaceutically acceptable salt thereof for the preparation of the purposes for the treatment of antihyperuricemic disease drug, and a kind of pharmaceutical composition for the treatment of hyperuricemia and gout.
The object of the invention is to be achieved through the following technical solutions:
Ellagic Acid Derivatives shown in following formula and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Shown in a kind of following formula 3,3 ' dimethoxy ellagic acid and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
3 methoxyl group ellagic acids shown in following formula and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
3 ' methoxyl group shown in following formula is tanned and is spent sour 4 O β D xylopyranoside and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
4 O shown in following formula (4 " O Galla Turcica (Galla Helepensis) acyl base α L rhamnopyranosyl) ellagic acid and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
4 O shown in a kind of following formula (3 ", 4 " the two Galla Turcica (Galla Helepensis) acyl base α L rhamnopyranosyl of O ) ellagic acid and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Shown in a kind of following formula 3,3 ', 4 ' trimethoxy ellagic acid and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Shown in a kind of following formula 3,3 ' dimethoxy is tanned and is spent sour 4 ' O β D xylopyranoside and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Shown in a kind of following formula 3,3 ' dimethoxy is tanned and is spent sour 4 ' O β D pyranglucoside and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
The present invention also provides a kind of pharmaceutical composition being used for the treatment of hyperuricemia, containing Ellagic Acid Derivatives of the present invention and pharmaceutically acceptable salt thereof in described pharmaceutical composition.
Described pharmaceutical composition also comprises pharmaceutically acceptable carrier.
Described pharmaceutical composition adds customary adjuvant, conveniently technique and makes clinical acceptable tablet, capsule, soft capsule, oral solutions, powder, drop pill, granule or injection.
Described hyperuricemia comprises the gout and gout complication that hyperuricemia causes.
Described gout complication comprises gouty arthritis, gouty nephropathy, lithangiuria or cardiovascular disease.
The invention has the advantages that:
Ellagic acid compounds of the present invention not only demonstrates stronger In-vitro Inhibitory Effect to xanthine oxidase, also can obviously reduce the serum uric acid level suffering from hyperuricemia mice, and have no side effect, safety is high, therefore can be used as the treatment of gout that potential xanthine oxidase inhibitor and uric acid resisting medicine cause for hyperuricemia and hyperuricemia or gout complication.More outstanding, the in vitro and in vivo active function of ellagic acid compounds of the present invention is all significantly better than several ellagic acid and the derivant of bibliographical information.
Detailed description of the invention
In order to make object of the present invention, technical scheme and advantage clearly understand, below in conjunction with embodiment, the present invention is further elaborated.Should be appreciated that specific embodiment described herein only in order to explain the present invention, be not intended to limit the present invention.
Ellagic acid and derivant are the qualified products that purity is greater than 98%; Fructus Terminaliae Billericae, Fructus Chebulae and the buying of Stem Bark of Sapium sebiferum medical material are from medical material market, Bozhou.
Embodiment 1 the compounds of this invention 2 5 extraction and sign
Get Fructus Terminaliae Billericae medical material 5kg, pulverize, alcohol reflux with 95% of 50L 3 times, each 3 hours, merge extractive liquid, 40 DEG C of concentrating under reduced pressure, extractum n-hexane extraction, after removing lipid, use Sephadex LH 20 carry out column chromatography, use 0% respectively, 5%, 10%, 20%, 30%, 50%, the ethanol of 100% carries out gradient elution and collects each elution fraction, by 5%, 10%, 20%, 30%, 50% elution fraction concentrating under reduced pressure is except after desolventizing, anti-phase C18 chromatographic column is used to carry out column chromatography respectively, use 0%, 5%, 25%, 50%, 100% methanol containing 2% acetic acid carries out eluting, collect eluent, concentrating under reduced pressure is except desolventizing, can obtain 2 5 four kinds of compounds, with HPLC – ESI MS and NMR detect, compound 2 5 its to detect characterization datas as follows:
Compound 1:(S) Flavogallonic acid C
21h
10o
13[M H]
: 468.9
1H‐NMR(CD
3OD,500MHz)δ:7.533(1H,),7.263(1H,)
13C‐NMR(CD
3OD,125MHz)δ:108.77,111.70,114.86,119.07,122.08,126.14,137.14,139.01,140.83,144.57,147.54,160.38,161.92.
Compound 2:3,3 ’ dimethoxy ellagic acid C
16h
10o
8[M H
]: 329.2
1H‐NMR(DMSO‐d
6,500MHz)δ:7.51(2H,s),4.04(6H,s)
13C‐NMR(DMSO‐d
6,125MHz)δ:60.92,111.40,111.71,112.14,140.19,141.23,152.04,158.39.
Compound 3:3 methoxyl group ellagic acid C
15h
8o
8[M H
]: 315.1
1H‐NMR(DMSO‐d
6,500MHz)δ:7.53(2H,s),4.0814.04(3H,s)
13C‐NMR(DMSO‐d
6,125MHz)δ:61.24,108.13,110.82,112.45,112.74,136.65,139.90,140.64,141.99,148.48,159.30.
Compound 4:3 ’ methoxyl group Rou Hua Suan 4 O β D xylopyranoside C
20h
16o
12[M H
]: 447.2
1H‐NMR(DMSO‐d
6,500MHz)δ:7.64(1H),7.48(1H),4.15(3H),4.87(1H),3.56(1H),3.50(1H),3.62(1H),3.45(1H),4.01(1H)
13C‐NMR(DMSO‐d
6,125MHz)δ:116.60,138.40,150.72,113.49,103.19,161.68,113.70,142.99,141.57,153.62,112.56,114.90,161.48,62.00,104.56,74.64,77.26,71.08,67.14.
The extraction of embodiment 2 the compounds of this invention 5,6 and sign
Get Fructus Chebulae's medical material 2kg, pulverize, alcohol reflux with 95% of 20L 3 times, each 3 hours, merge extractive liquid, 40 DEG C of concentrating under reduced pressure, extractum n-hexane extraction, after removing lipid, use Sephadex LH 20 carry out column chromatography, use 5% respectively, 15%, 25%, 35%, 60%, the ethanol of 100% carries out gradient elution and collects each elution fraction, by 5%, 15% elution fraction concentrating under reduced pressure is except after desolventizing, anti-phase C18 chromatographic column column chromatography is used to carry out purification respectively, use 5%, 15%, 25%, 50, 100% methanol containing 2% acetic acid carries out eluting, collect eluent, concentrating under reduced pressure is except desolventizing, can 5 be obtained, 6 two kinds of compounds, with HPLC – ESI MS and NMR detect, compound 5, 6 its detection characterization datas are as follows:
Compound 54 O (4 ” O Galla Turcica (Galla Helepensis) Xian Ji α L rhamnopyranosyl) ellagic acid
C
27H
20O
16[M‐H
‐]:599.0
1H‐NMR(CD
3OD,500MHz)δ:5.637(1H),4.297(1H),4.317(1H),5.250(1H,),4.036(1H),1.190(3H),7.834(1H),7.462(1H),7.095(2H)
13C‐NMR(CD
3OD,100MHz)δ:101.44,71.95,70.21,75.26,69.29,18.02,116.25,137.90,143.87,147.93,113.40,108.35,161.29,113.36,137.91,141.36,150.13,111.68,109.66,161.18,121.34,110.19,146.49,139.90,168.10.
Compound 64 O (3 ", 4 ” O two Galla Turcica (Galla Helepensis) Xian Ji α L rhamnopyranosyl) ellagic acid C
34h
24o
20] M H
]: 751.1
1H‐NMR(CD
3OD,500MHz)δ:5.69(1H),4.57(1H),5.66(1H),5.59(1H,),4.25(1H),1.27(3H),7.89(1H),7.48(1H),7.07(2H),7.02(2H)
13C‐NMR(CD
3OD,100MHz)δ:101.75,69.79,73.58,72.39,69.47,18.01,116.64,138.06,144.34,147.87,113.98,138.15,142.04,150.38,111.70,109.38,161.34,120.96,110.63,146.43,140.23,167.76.
Embodiment 3 the compounds of this invention 7,8, the extraction of 9 and sign
Get Chinese tallow tree medical material 3kg, pulverize, the alcohol reflux with 95% of 30L 3 times, each 3 hours, merge extractive liquid, 40 DEG C of concentrating under reduced pressure, extractum uses petroleum ether respectively, ethyl acetate, n-butyl alcohol extracts, after Ethyl acetate fraction concentrating under reduced pressure is gone out desolventizing, be repeatedly separated with silica gel column chromatography, use chlorine to imitate methanol elution gradient (V
chloroform: V
methanol=98: 2-70:30), recrystallization purifying is entered at gained position, can obtain compound 7,8,9.With HPLC – ESI MS and NMR detect, compound 7,8,9 its detect characterization datas as follows:
Compound 7:3,3 ', 4 ’ trimethoxy ellagic acid C
17h
12o
8[M H
]: 343.2
1H‐NMR(DMSO‐d
6,300MHz)δ:7.55(1H),7.64(1H),4.05(3H),4.06(3H,),4.01(3H)
13C‐NMR(DMSO‐d
6,75MHz)δ:111.2,140.9,140.2,152.6,111.6,111.9,158.2,112.4,141.6,140.8,153.7,107.5,113.4,158.5,60.9,61.3,56.6.
Compound 8:3,3 ’ dimethoxy Rou Hua Suan 4 ’ O β D xylopyranoside C
21h
18o
12[M H
]: 461.3
1H‐NMR(DMSO‐d
6,300MHz)δ:7.55(1H),7.76(1H),4.05(3H),4.08(3H,),5.17(1H)
13C‐NMR(DMSO‐d
6,75MHz)δ:111.2,140.9,140.2,151.2,111.5,111.7,158.3,114.2,141.6,141.9,152.7,111.9,112.7,158.4,61.0,61.6,101.8,72.9,76.0,69.2,65.7.
Compound 93,3 ’ dimethoxy Rou Hua Suan 4 ’ O β D pyranglucoside C
22h
20o
13[M H
]: 491.1
1H‐NMR(DMSO‐d
6,300MHz)δ:8.12(1H),8.54(1H),4.26(3H).
13C‐NMR(DMSO‐d
6,75MHz)δ:111.8,141.9,141.4,152.6,112.9,113.1,159.1,142.4,154.4,113.2,159.2,61.4,61.9,103.5,74.9,79.2,71.1,78.6,62.4.
Embodiment 4: ellagic acid compounds is to the In-vitro Inhibitory Effect of xanthine oxidase
For evaluating test-compound to the impact of xanthine oxidase, with 100% Febustat for positive controls, ellagic acid, ellagic acid compounds 1 9 to investigate for sample sets.
The external impact on xanthine oxidase of this experimentation, concrete grammar is as follows:
Solution preparation:
Phosphate buffered solution: the K taking 19.48g
2hPO
4.3H
2the KH of O and 1.99g
2pO
4be dissolved in 500mL distilled water, be made into the phosphate buffered solution (pH=7.5) that concentration is 0.2mmol/L;
Xanthine substrate solution: take xanthine 15.2mg, is dissolved in 250mL distilled water, is made into the xanthine substrate solution that concentration is 0.4mmol/L;
Xanthine oxidase solution: get xanthine oxidase 5U, is diluted to 160mL by above-mentioned phosphate buffered solution, is made into the xanthine oxidase solution that concentration is 80U/L, 4 DEG C of preservations;
Sample and positive control solution: precision takes sample sets, Febustat (as positive control), respectively with dimethyl sulfoxine dissolving, distilled water diluting, be made into concentration be 0.01 μm of ol/L the solution of variable concentrations of 2 μm of ol/L carry out testing that (wherein the ultimate density of dimethyl sulfoxine is less than 1%, when sample sets concentration does not reach required inhibition, concentration doubles to reconfigure).
Inhibitory action is tested:
Sample sets is tested: in 2mL centrifuge tube, add xanthine substrate solution 200 μ L, sample solution 100 μ L and xanthine oxidase solution 200 μ L successively, vortex shakes within 5 seconds, to be placed in 25 DEG C of water-baths and reacts 5 minutes, add 1.5mL dehydrated alcohol after completion of the reaction, vortex shakes 5 seconds cessation reactions.Reactant liquor centrifugal 5 minutes through 3500rpm, draw in 200 μ L to 1.5mL centrifuge tubes, detect the UA value of each sample by biochemistry analyzer respectively, each sample parallel operates three times and averages.
Blank group is tested: in 2mL centrifuge tube, add xanthine substrate solution 200 μ L, phosphate buffered solution 100 μ L and xanthine oxidase solution 200 μ L successively, and detect the UA value of blank group with method, operation repetitive is averaged for three times.
Positive controls is tested: in 2mL centrifuge tube, add xanthine substrate solution 200 μ L, positive control solution 100 μ L and xanthine oxidase solution 200 μ L successively, and detect the UA value of positive controls with method, operation repetitive is averaged for three times.
Test result:
According to xanthine oxidase suppression ratio=[(blank group UA value-sample sets UA value)/blank group UA value] * 100, calculate suppression ratio; Drug level C=C in enzymatic reaction
0* 0.1/3.1 (C
0for sample solution concentration); Drug level and suppression ratio are returned, obtains regression equation; C value when being 50% according to regression equation calculation suppression ratio, i.e. half-inhibition concentration IC
50, result is as shown in table 1.
Table 1 compound is to the In-vitro Inhibitory Effect (IC of xanthine oxidase
50, μm ol/L)
Table 1 result shows, Ellagic Acid Derivatives of the present invention all than the ellagic acid of bibliographical information, Rou Hua Suan 4 O β D xylopyranoside embody stronger In-vitro Inhibitory Effect, wherein compound 1,2,5,6,7 inhibit activities are better, especially compound 1,5,6 is suitable with the xanthine oxidase inhibitory action of positive control Febustat, has very high inhibit activities, can be used as the treatment of potential xanthine oxidase inhibitor for hyperuricemia.
Embodiment 5: Ellagic Acid Derivatives is on the impact of the serum uric acid level of reduction hyperuricemia mice
The present embodiment is by zoopery checking compound on the impact of hyperuricemia mice, and with 100% Febustat for positive controls, ellagic acid, ellagic acid compounds 1,2,5,7,9 are investigated for sample sets.
Experimental animal and grouping: healthy male KM mice 100, body weight is 15 18g, and by Shanghai, Ling Chang bio tech ltd provides;
After only carrying out point cage process by every cage 5, raise 4 days at the barrier system endoadaptation of company, 90 mices choosing body weight concentrated from 100 mices are divided into 9 groups by body weight stochastic averagina, often organize 10, be respectively blank group, hyperuricemia model group, positive controls, given the test agent group.
The modeling of hyperuricemia:
Immediately gastric infusion is carried out to mice after the laundering period, every morning gavage 1 time, wherein test-compound pure water carries out suspendible, carries out gavage according to 10mg/kg; Positive control Febustat pure water carries out suspendible, carries out gavage according to 1.0mg/kg; Blank group and hyperuricemia model group all contrast by pure water gavage, continuous gavage 7 days;
The 7th day morning gavage after 0.5 hour, lumbar injection modeling is carried out to mice, wherein blank group lumbar injection 0.5% sodium carboxymethyl cellulose (CMC Na) solution; Hyperuricemia model group, positive controls and given the test agent group injection Oteracil Potassium (OA), with CMC Na solution dissolve, injection volume is 300mg/kg body weight;
Lumbar injection extracts mice eyeball after 1.5 hours is taken a blood sample, blood sampling capacity is not less than 0.5mL, place about 1 hour in room temperature after blood specimen collection, after blood solidifies completely under 3500rpm/4 DEG C of condition centrifugal 10 minutes, get serum under equal conditions multiple from 5 minutes, then get 0.2mL serum and use biochemistry analyzer to detect UA value;
With Excel and SPSS, statistical analysis is carried out to data, calculate average and SD, the group difference of more each experimental group after one factor analysis of variance, compared with blank group, the serum uric acid level of hyperuricemia model group, positive controls and test-compound group mice significantly improves, there is significant difference, show modeling success.
Table 2 compound is on the impact (μm ol/L) of hyperuricemia mice serum uric acid level
Note: (### represents and compares P<0.001 with blank group; * represent compared with hyperuricemia model group, P<0.05; * represents and compares P<0.01 with model group; * * represent compare P<0.001 with model group)
Found out by table 2 result, compound of the present invention all demonstrate be better than bibliographical information ellagic acid, Rou Hua Suan 4 O β D xylopyranoside body in uric acid resisting effect, and embody uric acid resisting effect in significant body, and wherein compound 1 and compound 7 effect can be used as more by force the treatment of potential uric acid resisting medicine for hyperuricemia.
Embodiment 6: the medicinal composition tablets of ellagic acid compounds or its pharmaceutically acceptable salt
[prescription 1]
[prescription 2]
[prescription 3]
Take ellagic acid compounds or its pharmaceutically acceptable salt, starch and the L-HPC of recipe quantity, mixing, cross 60 mesh sieve three times, mix homogeneously; Add the starch slurry soft material processed in right amount of 10%, granulate, dry, after granulate, add micropowder silica gel, magnesium stearate mix homogeneously, tabletting, film coating, to obtain final product.
Embodiment 7: the medicament composition capsule agent of ellagic acid compounds or its pharmaceutically acceptable salt
[prescription 1]
[prescription 2]
[prescription 3]
Take ellagic acid compounds or its pharmaceutically acceptable salt, the above-mentioned adjuvant of recipe quantity, cross 60 mesh sieve three times, mix homogeneously, incapsulates and get final product.
Obviously, above-described embodiment is only for clearly example being described, and the restriction not to embodiment.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without the need to also giving all embodiments.And thus the apparent change of extending out or variation be still among the protection domain of the invention.
Claims (10)
1. the Ellagic Acid Derivatives shown in following formula: compound 1 and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
2. 3,3 ' dimethoxy ellagic acid shown in a following formula: compound 2 and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Or 3 methoxyl group ellagic acids shown in a kind of following formula: compound 3 and pharmaceutically acceptable salt thereof the purposes in preparation treatment antihyperuricemic disease drug,
3. 3 ' methoxyl group shown in following formula: compound 4 is tanned and is spent sour 4 O β D xylopyranoside and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
4. 4 O shown in following formula: compound 5 (4 " O Galla Turcica (Galla Helepensis) acyl base α L rhamnopyranosyl) ellagic acid and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Or 4 O shown in a kind of following formula: compound 6 (3 ", 4 " the two Galla Turcica (Galla Helepensis) acyl base α L rhamnopyranosyl of O ) ellagic acid and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
5. 3,3 ', 4 ' trimethoxy ellagic acid shown in a following formula: compound 7 and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
6. 3,3 ' dimethoxy shown in a following formula: compound 8 is tanned and is spent sour 4 ' O β D xylopyranoside and the purposes of pharmaceutically acceptable salt in preparation treatment antihyperuricemic disease drug thereof,
Or 3,3 ' dimethoxy shown in a kind of following formula: compound 9 is tanned and is spent sour 4 ' O β D pyranglucoside and pharmaceutically acceptable salt thereof the purposes in preparation treatment antihyperuricemic disease drug,
7. according to claim 1 6 arbitrary described purposes, it is characterized in that, described medicine also comprises pharmaceutically acceptable carrier.
8. according to claim 1 6 arbitrary described purposes, it is characterized in that, described medicine adds customary adjuvant, conveniently technique and makes clinical acceptable tablet, capsule, soft capsule, oral solutions, powder, drop pill, granule or injection.
9. according to claim 1 6 arbitrary described purposes, it is characterized in that, described hyperuricemia comprises the gout and gout complication that hyperuricemia causes; Described gout complication comprises gouty arthritis, gouty nephropathy, lithangiuria or cardiovascular disease.
10. be used for the treatment of a pharmaceutical composition for hyperuricemia, it is characterized in that, containing, for example the arbitrary described compound of claim 1 6 and pharmaceutically acceptable salt thereof in described pharmaceutical composition.
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| CN109966304A (en) * | 2018-04-23 | 2019-07-05 | 西南医科大学 | Garden burnet active constituent is preparing the purposes in wound healing drug |
| CN111333662A (en) * | 2020-04-09 | 2020-06-26 | 西南医科大学 | 3,4' -O-dimethyl gallic acid, its derivative and pharmaceutical use thereof |
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| BEATE PFUNDSTEIN等: "Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): Characterization,quantitation and determination of antioxidant capacities", 《PHYTOCHEMISTRY》 * |
| BRUNO FOGLIANI等: "Bioactive ellagitannins from Cunonia macrophylla, an endemic Cunoniaceae from New Caledonia", 《PHYTOCHEMISTRY》 * |
| DAISUKE KADOWAKI等: "Direct Radical Scavenging Activity of Benzbromarone Provides Beneficial Antioxidant Properties for Hyperuricemia Treatment", 《BIOL. PHARM. BULL.》 * |
| ZENGJUN GUO等: "Antioxidant and cytotoxic activity of the acetone extracts of root of Euphorbia hylonoma and its ellagic acid derivatives", 《JOURNAL OF MEDICINAL PLANTS RESEARCH》 * |
| ZHI-HONG ZHOU等: "A new ellagic acid derivative from polygonum runcinatum：Formerly Natural Product Letters", 《NATURAL PRODUCT RESEARCH》 * |
| 刘又豪等: "桉叶提取物抑制黄嘌呤氧化酶活性成分的分离纯化及其动力学研究", 《广东农业科学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109966304A (en) * | 2018-04-23 | 2019-07-05 | 西南医科大学 | Garden burnet active constituent is preparing the purposes in wound healing drug |
| CN111333662A (en) * | 2020-04-09 | 2020-06-26 | 西南医科大学 | 3,4' -O-dimethyl gallic acid, its derivative and pharmaceutical use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105012294B (en) | 2017-08-25 |
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